The Role of Genes

The most fundamental patterns of an individual's phenotype are influenced by a combination of the person's genotype and the environment. Genes are segments of DNA that act as molecular blueprints dictating the development and organization of cells that eventually make up tissues, organs and structures of the human body. During development, there are periods when sensitivity to environmental influences increases based on genetic predisposition. These outside influences serve either to promote or to interfere with normal development.

     A series of homeotic genes known as Hox genes are known to play an important role in craniofacial development. These sequences of genes act as regulators of other genes; when they are affected, the function of other genes are affected. This is known as "cascading." Such cascades of gene action are known to act in skull development. Determination of upstream and downstream effects of gene action is a major goal of molecular biological studies, due primarily to the fact that a mutation in a single gene can cause a suite of anomalies in various bodily systems.
      Several Hox genes are known to control the formation of individual elements of the skull. In order to better understand the mechanisms of specific genes in human skull development, other less complex animal and insect models have been studied. For example, the fruitflies, mice, fish, and frogs are used as study models for comparing gene activation and expression in humans. It appears that humans, utilize some of the same gene regulation schemes that lesser organisms use to control similar developmental processes (Larsen, 1997).

For a more in-depth look at specific genes andtheir related disorder or syndrome please look at our Research section of the Center for Craniofacial Development and Disorders web site or check out our Related Links page.

Environmental Factors

     Not all craniofacial disorders are direct results of inheriting specific genes. There are many known teratogens, harm-inducing substances or environmental conditions, that are linked to congenital skull defects. These teratogens may potentially mutate, or alter, the expression of genes, and in turn affect the subsequent development of the phenotype.
     A major teratogen is alcohol, which indirectly affects the formation of the skull by hindering development of the brain. The close relation between the formation of the brain and the skull is very delicate and interdependent; problems in one can result in deformation of the other.
     However, not all craniofacial disorders are compound or dependent on each other. For example, some defects in the formation of the eye and the ear can occur independently from the larger defects in facial development (Sweeney, 1998). Other environmental influences on later skull development can be attributed to infection, malnutrition, mechanical stress during pregnancy or childbirth.

As a group of disorders, craniofacial abnormalities are numerous and varied. In many cases the environmental and genetic situations that cause a specific craniofacial defect are known. However, there is much overlap between types of abnormalities, and the causes can often be a complex combination of genetic and environmental factors.

Of the approximately 5,000 known human inherited conditions, over 700 are craniofacial abnormalities. Two major categories of common craniofacial disorders are craniosynostosis (the premature fusion of skull bones) and oral clefting.

Figure 1 is an example of isolated craniosynostosis. Here, the one of the left coronal suture has fused prematurely, creating abnormal development of the skull. 

For more informtion, take a look at major developmental disorders in the Skull Vault disorders section or Oral and Facial region disorders section other major craniofacial disorders, see our section on Disorders of Development.